This invention relates to preparation of acyloxy furans and thiophenes which undergo rearrangement in the presence of Lewis acids, using as starting materials butenolides. Prior to this invention, and my invention disclosed and claimed in co-pending U.S. application Ser. No. 966,268, entitled ALKOXY OR ACYLOXY FURANS FROM BUTENOLIDES, field Dec. 4, 1978, there has been no reasonable synthetic method for the general preparation of acyloxy furans. In my prior application, the butenolide ring is first treated with alkylating agents, such as trialkyl chlorosilanes in the presence of a strong organic base, and thereafter the alkylated furan ring is reacted with an organic electrophile to provide addition of the electrophile to the alpha position of the furan ring.
In accordance with the present invention in the first step of the reaction, acylating agents are utilized. It has been discovered that when acylating agents are employed in the first step reaction synthesis, followed by a catalytic reaction with Lewis acids, a novel and unexpected arrangement to form compounds of the class known as keto-lactones are prepared. These compounds have been previously unreported in the literature and offer avenues to synthesis of a wide variety of active compounds.
As those skilled in the art know and understand, furan compounds are those which contain at some point in the compound's structure the following common nucleus: ##STR1##
Such furan ring containing compounds are valuable precursors for the preparation of a wide variety of biologically active compounds. They can, for example, be successfully used as the starting point for preparation of complex butenolides, of other substituted furans, and they can be used for the making of such biologically active compounds, such as lycorine which is an anti-bacterial agent whose structure represents a challenge to present methods of synthesis, gibberelic acid, which is an important plant growth regulator that is not easily available from natural sources, and protoanemonin and its substituted derivatives, among others. In short, the number of desirable biologically active compounds which can be prepared using as a nucleus the furan moiety is almost limitless.
However, the effective utilization of furans as a precursor for preparation the numerous desirable biologically active compounds such as those listed above has met with only limited success and usage in the past. This is so primarily because of the difficulty of obtaining the furan starting materials.
Accordingly a primary object of this invention is to provide a synthesis process which allows for quick, easy high yield preparation of furan compounds.
Another object of the invention is to provide a synthetic process for preparation of furans which in turn can be used as building blocks for preparing a wide variety of biologically active compounds.
Yet another object of this invention is to provide an intermediate class of furans which are prepared from readily available butenolides as a starting material and which under the conditions of the reaction of this invention, undergo rearrangement to provide an intermediate furan ring. The intermediate furan ring itself is then reacted in the presence of catalytically effective amounts of Lewis acids to provide an additional rearrangement which is unexpected, unreported in the literature, and provides not only novel compounds, but novel compounds which are highly useful biologically active compounds in and of themselves; and which further can, in turn, be used as starting materials to achieve synthesis of a wide variety of compounds which previously have not been available by conventional laboratory synthesis.
The method and manner of accomplishing these objects of the invention, as well as others, will become apparent from the detailed description of the invention which follows.